Definition Of Sepsis Research Articles

Oxygen Targets for Mechanically Ventilated Adults with Sepsis: Secondary Analysis of the PILOT Trial.

Patients with sepsis frequently require invasive mechanical ventilation. How oxygenation during mechanical ventilation affects clinical outcomes for patients with sepsis remains uncertain. To evaluate the effects of different oxygen saturation targets on clinical outcomes for patients with sepsis receiving mechanical ventilation. We performed a secondary analysis of the Pragmatic Investigation of optimaL Oxygen Targets (PILOT) trial dataset among patients who met criteria for sepsis by the Sepsis-3 definition at the time of enrollment. We compared patients randomized to a lower oxygen saturation target (90%; range, 88-92%), an intermediate target (94%; range, 92-96%), and a higher target (98%; range, 96-100%) with regard to the outcomes of 28-day in-hospital mortality and ventilator-free days to study day 28. Of 2541 patients in the PILOT dataset, 805 patients with sepsis were included in the current analysis. In-hospital mortality by day 28 did not differ significantly between the lower target group (48%; 95% confidence interval [CI], 42% to 54%), the intermediate target group (50%; 95% CI, 43% to 56%), and the higher target group (51%; 95% CI, 45% to 56%) (P = 0.83). The number of ventilator-free days to day 28 did not significantly differ between the trial groups, with a mean of 9.9 (standard deviation [SD], 11.8) in the lower oxygen saturation target group, 9.5 (SD, 11.2) in the intermediate group, and 9.4 (SD, 11.4) in the higher group (P = 0.65). Among mechanically ventilated patients with sepsis in a large, randomized trial, the incidence of 28-day in-hospital mortality was not statistically significantly different between the use of a lower, intermediate, or higher oxygen target. However, the confidence intervals included treatment effects that would be clinically meaningfully and further randomized trials of oxygen targets in sepsis are required. Pragmatic Investigation of optimaL Oxygen Targets Trial (PILOT)ClinicalTrials.gov number NCT03537937URL: https://clinicaltrials.gov/study/NCT03537937.

Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey.

Early detection, standardized therapy, adequate infrastructure and strategies for quality improvement should constitute essential components of every hospital's sepsis plan. To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute hospitals. A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals. This included the use of sepsis definitions, the implementation of sepsis guideline recommendations, diagnostic and therapeutic infrastructure, antibiotic stewardship, and quality improvement initiatives in hospitals. 1023 hospitals in 69 countries were included. Most of them, 835 (81.6%) were from Europe. Sepsis screening was used in 54.2% of emergency departments(EDs), 47.9% of wards, and 61.7% of intensive care units(ICUs). Sepsis management was standardized in 57.3% of EDs, 45.2% of wards and in 70.7% of ICUs. The implementation of comprehensive quality improvement initiatives(QIIs) was associated with increased screening (EDs +33.3%; wards +44.4%; ICUs +23.8% absolute difference) and increased standardized sepsis management (EDs +33.6%; wards +40.0%; ICUs: +17.7% absolute difference) compared to hospitals without QIIs. 9.8% of hospitals had implemented ongoing QIIs, and 4.6% had invested in sepsis programs. The findings indicate that there is considerable room for improvement in a large number of mainly European hospitals, particularly with regards to early identification and standardized management of sepsis, the availability of guidelines, diagnostic and therapeutic infrastructure, and the implementation of QIIs. Further efforts are required to implement a more comprehensive and appropriate quality of care.

Left ventricular diastolic dysfunction is prevalent but not associated with mortality in patients with septic shock.

Prognostic impact of left ventricular diastolic dysfunction (LVDD) in septic shock patients has not been determined using current diagnostic guidelines. We assessed the relation between LVDD during the first 3days following intensive care unit (ICU) admission for septic shock and Day-28 mortality. This prospective, multicenter, observational study enrolled 402 patients (age: 63 ± 13year; 59% male; SAPS II: 59 ± 20; SOFA: 9.4 ± 3.6; mechanical ventilation: 74%) with septic shock (Sepsis-3 definition). Patients were echocardiographically assessed within 12h after admission (Day 1), on Day 2, Day 3, at ICU and at hospital discharge (or Day 28 whichever occurred first), using 2016 American-European guidelines. LVDD was present at least once between Day 1 and 3 in 304 patients (76%), and in 56% and 44% of patients at ICU discharge and on Day 28 (or hospital discharge), respectively (43% of patients with follow-up). Seventy-eight of 172 patients (45%) exhibited similar LV diastolic properties throughout the study period while 58 patients (34%) improved their LVDD at follow-up (lower grade: n = 9, regression: n = 49). Day-28 mortality was not statistically different between patients with and without LVDD (80/304 [26%] vs. 25/88 [28%]; OR: 0.900 [0.530-1.527]; p = 0.696). Similar results were obtained when adjusting the multivariate model on SAPSII or SOFA score on admission, together with fluid balance during the first three days of ICU stay (OR: 0.838 [0.471-1.491]: p = 0.547 and OR: 0.887 [0.513-1.534]: p = 0.668, respectively). LVDD was highly prevalent in patients with septic shock but not associated with mortality. It appeared improving in one-third of survivors. PRODIASYS study registered on ClinicalTrials (September 27, 2016, number NCT02918214).

PROGNOSTIC ACCURACY OF MACHINE LEARNING MODELS FOR IN-HOSPITAL MORTALITY AMONG CHILDREN WITH PHOENIX SEPSIS ADMITTED TO THE PEDIATRIC INTENSIVE CARE UNIT.

Objective: The Phoenix sepsis criteria define sepsis in children with suspected or confirmed infection who have ≥2 in the Phoenix Sepsis Score. The adoption of the Phoenix sepsis criteria eliminated the Systemic Inflammatory Response Syndrome criteria from the definition of pediatric sepsis. The objective of this study is to derive and validate machine learning models predicting in-hospital mortality for children with suspected or confirmed infection or who met the Phoenix sepsis criteria for sepsis and septic shock. Materials and Methods: Retrospective cohort analysis of 63,824 patients with suspected or confirmed infection admission diagnosis in two pediatric intensive care units (PICUs) in Atlanta, Georgia, from January 1, 2010, through May 10, 2022. The Phoenix Sepsis Score criteria were applied to data collected within 24 h of PICU admission. The primary outcome was in-hospital mortality. The composite secondary outcome was in-hospital mortality or PICU length of stay (LOS) ≥ 72 h. Model-based score performance measures were the area under the precision-recall curve (AUPRC) and the area under the receiver operating characteristic curve (AUROC). Results: Among 18,389/63,824 (29%) children with suspected infection (median age [25th - 75th interquartile range [IQR]): 3.9 [1.1,10.9]; female, 45%, a total of 5,355 met Phoenix sepsis criteria within 24 h of PICU admission. Of the children with Phoenix sepsis, a total of 514 (9.6%) died in the hospital, and 2,848 (53.2%) died or had a PICU stay of ≥72 h. Children with Phoenix septic shock had an in-hospital mortality of 386 (16.4%) and 1,294 (54.9%) had in-hospital mortality or PICU stay of ≥72 h. For children with Phoenix sepsis and Phoenix septic shock, the multivariable logistic regression, light gradient boosting machine, random forest, eXtreme Gradient Boosting, support vector machine, multilayer perceptron, and decision tree models predicting in-hospital mortality had AUPRCs of 0.48-0.65 (95% CI range: 0.42-0.66), 0.50-0.70 (95% CI range: 0.44-0.70), 0.52-0.70 (95% CI range: 0.47-0.71), 0.50-0.70 (95% CI range: 0.44-0.70), 0.49-0.67 (95% CI range: 0.43-0.68), 0.49-0.66 (95% CI range: 0.45-0.67), and 0.30-0.38 (95% CI range: 0.28-0.40) and AUROCs of 0.82-0.88 (95% CI range: 0.82-0.90), 0.84-0.88 (95% CI range: 0.84-0.90), 0.81-0.88 (95% CI range: 0.81-0.90), 0.84-0.88 (95% CI range: 0.83-0.90), 0.82-0.87 (95% CI range: 0.82-0.90), 0.80-0.86 (95% CI range: 0.79-0.89), and 0.76-0.82 (95% CI range: 0.75-0.85), respectively. Conclusion: Among children with Phoenix sepsis admitted to a PICU, the random forest model had the best AUPRC for in-hospital mortality compared to the light gradient boosting machine, eXtreme Gradient Boosting, logistic regression, multilayer perceptron, support vector machine, and decision tree models or a Phoenix Sepsis Score ≥ 2. These findings suggest that machine learning methods to predict in-hospital mortality in children with suspected infection predict mortality in a PICU setting with more accuracy than application of the Phoenix sepsis criteria.

Neonatal Sepsis: A Comprehensive Review

Neonatal sepsis remains a significant cause of neonatal morbidity and mortality globally. At present, no clear consensus definition for sepsis in neonates exists, even though a positive blood culture is considered as the gold standard for definitive diagnosis. The accurate and timely diagnosis of sepsis in neonates presents significant difficulties, since “culture negative” or “suspected” sepsis varies widely worldwide. Antibiotic overuse and resistance are emerging problems, but on the other hand, under-recognition of sepsis and delayed antibiotic treatment could have serious or even fatal adverse outcomes in this vulnerable population. In the context of rapid recognition of sepsis and timely initiation of appropriate antibiotic therapy, various sepsis risk assessment tools have been developed, a variety of biomarkers are in clinical use or under research for future use, and new diagnostic techniques are under evaluation. In this review, we summarize the most recent data on neonatal sepsis, the utility of sepsis risk assessment tools for term and preterm infants with sepsis, and current diagnostic and preventive tools.

Mediating Role of Platelet Count Increase in Unfractionated Heparin Treatment for Sepsis Patients: A Retrospective Cohort Analysis

Aims/Background The role of heparin in sepsis therapy has been widely debated. The controversy surrounding heparin’s use as an anticoagulant in sepsis may stem from differences in sepsis definitions, study designs, timing and dosage of drug administration, treatment duration, complications, and patient severity. In this study, we aimed to determine the optimal timing and dosage of heparin in patients with sepsis, identify specific subgroups that could benefit from heparin therapy, and explore laboratory markers to assess its efficacy. Methods This retrospective cohort study was conducted using the Medical Information Mart for Intensive Care-IV dataset. Data from patients with sepsis were extracted based on the Sepsis 3.0 criteria. Patients were categorized according to heparin use. The effectiveness of early and appropriate heparin administration was assessed, and a subgroup analysis was performed to identify patients most likely to benefit from heparin therapy. Additionally, factors mediating the improvement in sepsis prognosis following heparin treatment were analyzed. Results We recruited 4149 participants who met the inclusion criteria, with an overall 28-day mortality rate of 19.5%. There were 2192 individuals in the heparin group and 1957 in the non-heparin group. After propensity score matching, heparin therapy demonstrated a significantly greater effect on reducing both 28-day and 90-day mortality compared to the non-heparin treatment (18.1% vs. 10.7%, p < 0.001; 18.8% vs. 12.6%, p < 0.001). However, the heparin group had a higher incidence of major bleeding (10.9% vs. 6.3%, p = 0.001), increased use of mechanical ventilation (54.3% vs. 45.1%, p < 0.001), and a longer intensive care unit stay (3.6 vs. 2.5 days, p < 0.001) compared to the non-heparin group. Early administration of high-dose heparin improved 28-day survival. Early and adequate heparin administration was more effective than late and insufficient dosing (p < 0.01), except in patients with sepsis who had low white blood cell counts, alkalosis, or reduced platelet counts. The increase in platelet count had a significant mediating effect on the entire cohort (p < 0.001 for the causal mediation effect), with a mediation proportion of 14%. Conclusion Early and adequate heparin administration can significantly improve the prognosis of sepsis. An increase in platelet count may serve as a potential indicator of the effectiveness of heparin therapy in sepsis.

Sepsis Epidemiology and Outcomes in Pediatric Intensive Care Unit of Alkhadra Hospital, Tripoli, Libya

Despite the various interventions and therapies that have been implemented to improve the quality of life for children with sepsis, the prevalence and death rates continue to increase. This issue is a major public health problem that requires the continuous improvement of the guidelines and the identification of new strategies. The aim of the study was to identify the prevalence and outcomes of severe sepsis among children admitted to the Pediatric Intensive Care Unit (PICU). This study was conducted in PICU of Alkhadra Hospital in 2023 as a hospital-based retrospective study. All children who were admitted to the PICU from 2017 to 2022 were included. Data was collected from hospital file records, which included the following: age of patient, gender, comorbidities of patients, and source of admission; origin of sepsis; type of PICU admission; primary site of infection; organ dysfunction present at screening; and patient outcomes. Of the 1284 total admissions to the PICU, 128 patients (9.96%) met the definition of sepsis. Most patients (78.9%) were less than 6 years old. Respiratory problems and congenital malformations were the most common co-morbidities, with reported rates of 18.8% and 10.2%, respectively. The emergency department was the most common source of admission (67.2%). Nearly all patients had good overall performance, whereas (21.1%) of the patients were in a coma. 77.3% discharged during the study, and 22.7% died. Although decreasing the incidence through preventive measures is ideal, early recognition and treatment of sepsis will decrease both short- and long-term complications and related mortality of at-risk infants and children.

Beyond Early- and Late-onset Neonatal Sepsis Definitions: What are the Current Causes of Neonatal Sepsis Globally? A Systematic Review and Meta-analysis of the Evidence.

Sepsis remains a leading cause of neonatal mortality, particularly in low- and lower-middle-income countries (LLMIC). In the context of rising antimicrobial resistance, the etiology of neonatal sepsis is evolving, potentially making currently-recommended empirical treatment guidelines less effective. We performed a systematic review and meta-analysis to evaluate the contemporary bacterial pathogens responsible for early-onset sepsis (EOS) and late-onset neonatal sepsis (LOS) to ascertain if historical classifications-that guide empirical therapy recommendations based on assumptions around causative pathogens-may be outdated. We analyzed 48 articles incorporating 757,427 blood and cerebrospinal fluid samples collected from 311,359 neonates across 25 countries, to evaluate 4347 significant bacteria in a random-effects meta-analysis. This revealed gram-negative bacteria were now the predominant cause of both EOS (53%, 2301/4347) and LOS (71%, 2765/3894) globally. In LLMICs, the predominant cause of EOS was Klebsiella spp. (31.7%, 95% CI: 24.1-39.7%) followed by Staphylococcus aureus (17.5%, 95% CI: 8.5 to 28.4%), in marked contrast to the Streptococcus agalactiae burden seen in high-income healthcare settings. Our results reveal clear evidence that the current definitions of EOS and LOS sepsis are outdated, particularly in LLMICs. These outdated definitions may be guiding inappropriate empirical antibiotic prescribing that inadequately covers the causative pathogens responsible for neonatal sepsis globally. Harmonizing sepsis definitions across neonates, children and adults will enable a more acurate comparison of the epidemiology of sepsis in each age group and will enhance knowledge regarding the true morbidity and mortality burden of neonatal sepsis.

Adult Code Sepsis: A Narrative Review of its Implementation and Impact.

This narrative review explores the implementation and impact of sepsis code protocols, an urgent intervention strategy designed to improve clinical outcomes in patients with sepsis. We examined the degree of implementation, activation criteria, areas of implementation, personnel involved, responses after activation, goals and targets, impact on clinical indicators, and challenges in implementation. The reviewed evidence suggests that sepsis codes can significantly reduce sepsis-related mortality and enhance early administration of treatments. However, variability in activation criteria and inconsistent application present ongoing challenges. The review considers the incorporation of newer scoring systems, such as NEWS and MEWS, and the potential integration of machine learning tools for early sepsis detection. It highlights the importance of tailoring implementation to specific healthcare contexts and the value of ongoing training to optimize sepsis response. Limitations include the ongoing controversy surrounding sepsis definitions and the need for standardized, feasible quality indicators. Future research should focus on standardizing activation criteria, improving protocol adherence, and exploring emerging technologies to enhance early sepsis detection and management. Despite challenges, sepsis codes show promise in improving patient outcomes when implemented thoughtfully and consistently across healthcare settings.

Conceptual Model of Sepsis as a Dysregulated Host Response: Depicting Directionality of Immunologic and Metabolic Dysregulation.

Background Mortality from Sepsis continues to remain high in hospitalized patients worldwide. Previously, the conceptual model of sepsis was based on the systemic inflammatory immune response syndrome, an adaptive model. In 2016, a new definition of sepsis was proposed as a dysregulated host response to infection, however until now, no model has been proposed elucidating what immunologic mechanisms are dysregulated. Aim We sought to propose a new model of sepsis to elucidate evidence-based immunologic and metabolic mechanisms which are dysregulated in sepsis. Methods Evidence in the literature comparing and contrasting sepsis before and after the 2016 consensus definition of sepsis was reviewed for themes. Themes from research published post 2016, were described connecting immunologic and metabolic mechanisms in sepsis. This information further informed earlier research that has been published by the primary author. Results A new conceptual model of sepsis was developed to elucidate the current definition of sepsis as a dysregulated host response, incorporating themes uncovered in sepsis research post 2016. Conclusion The model proposed here supports clinicians in applying the current definition of sepsis to a physiological model. This can benefit clinicians by offering new ways of recognizing sepsis, and researchers by recommending a physiologic model to advance sepsis research. Keywords: Sepsis, sepsis model, immunologic dysregulation, metabolic dysregulation

Phoenix criteria for sepsis: are these enough to guide a clinician?

In conclusion, Phoenix criteria are a step in the right direction to define life-threatening organ dysfunction in sepsis, but clinicians need to be mindful that diagnosis/treatment of less severe sepsis should not be delayed if these criteria are not met. Therefore, local early detection and management tools for sepsis should be followed. • There has always been a quest for a definition for pediatric sepsis. There are limitations to the previous pediatric sepsis criteria which were published in 2005 by the International Pediatric Sepsis Consensus Conference (IPSCC). IPSCC defines sepsis as a suspected or confirmed infection in the presence of systemic inflammatory response syndrome (SIRS). These new Phoenix Pediatric Sepsis (PPS) criteria for sepsis and septic shock are intended to identify children with life-threatening organ dysfunction due to infection, and the score was developed based on a very large pediatric dataset. • Though the intention of Phoenix criteria is to help identify children with life threatening organ dysfunction, unfortunately the crietria will miss signs of early sepis. In this manuscript, we point out some of the drawbacks of these criteria which need to be borne in mind while applying these criteria.

Modulation of Metabolomic Profile in Sepsis According to the State of Immune Activation.

To investigate the metabolomic profiles associated with different immune activation states in sepsis patients. Subgroup analysis of the PROVIDE (a Personalized Randomized trial of Validation and restoration of Immune Dysfunction in severe infections and Sepsis) prospective clinical study. Results of the PROVIDE study showed that patients with sepsis may be classified into three states of immune activation: 1) macrophage-activation-like syndrome (MALS) characterized by hyperinflammation, sepsis-induced immunoparalysis, and 3) unclassified or intermediate patients without severe immune dysregulation. Two hundred ten patients from 14 clinical sites in Greece meeting the Sepsis-3 definitions with lung infection, acute cholangitis, or primary bacteremia. During our comparison, we did not perform any intervention. Untargeted metabolomics analysis was performed on plasma samples from 210 patients (a total of 1394 products). Differential abundance analysis identified 221 significantly different metabolites across the immune states. Metabolites were enriched in pathways related to ubiquinone biosynthesis, tyrosine metabolism, and tryptophan metabolism when comparing MALS to immunoparalysis and unclassified patients. When comparing MALS to unclassified, 312 significantly different metabolites were found, and pathway analysis indicated enrichment in multiple pathways. Comparing immunoparalysis to unclassified patients revealed only two differentially regulated metabolites. Findings suggest distinct metabolic dysregulation patterns associated with different immune dysfunctions in sepsis: the strongest metabolic dysregulation is associated with MALS.

Mortality prediction model from combined serial lactate, procalcitonin and calprotectin levels in critically ill patients with sepsis: A retrospective study according to Sepsis-3 definition

Objective1) To evaluate the ability of baseline and on 24 h serum calprotectin, in comparison to canonical biomarkers (lactate and procalcitonin), for prognosis of 28-day mortality in critically ill septic patients; and 2) To develop a predictive model combining the three biomarkers. DesignA single-center, retrospective study. SettingIntensive Care Unit of a university hospital. Patients or participantsOne hundred and seventy three septic pacientes were included. InterventionsMeasurement of baseline lactate, procalcitonin and calprotectin level and procalcitonin and calprotectin levels on 24 h. Main variables of interestDemographics and comorbidities, SOFA score on ICU admission, baseline lactate, procalcitonin and calprotectin on admission and on 24 h and 28-day mortality. Results1) On ICU admission, lactate was the only biomarker achieving a significant accuracy (AUC: 0.698); 2) On 24 h, no differences were found on procalcitonin and calprotectin levels. Procalcitonin and calprotectin clearances were significantly lower in non-survivors and both achieved a moderate performance (AUCs: 0.668 and 0.664, respectively); 3) A biomarker based-model achieved a significant accuracy (AUC: 0.766), trending to increase (AUC: 0.829) to SOFA score alone; y 4) Baseline lactate levels and procalcitonin and calprotectin clearance were independent predictors for the outcome. Conclusions1) Baseline and on 24 h calprotectina and procalcitonin levels lacked ability in predicting 28-day mortality; 2) Accuracy of clearance of both biomarkers was moderate; and 3) Combination of SOFA score and the predictive biomarker based-model showed a high prognostic accuracy.

Agreement Between Sepsis-2 and Sepsis-3 Definitions Among Patients Admitted to the Intensive Care Unit.

Agreement Between Sepsis-2 and Sepsis-3 Definitions Among Patients Admitted to the Intensive Care Unit.

Preserved left ventricular ejection fraction with abnormal myocardial work in sepsis

Abstract Background Sepsis is a life-threatening condition associated with a dysregulated response to infection, leading to an increased risk of multi-organ dysfunction and death. Left ventricular (LV) dysfunction has been reported in up to 60% of patients with sepsis. Still, it’s true incidence is difficult to determine as defined by standard methods like left ventricular ejection fraction (LVEF) due to its dependency on loading conditions. Myocardial work (MW) is a validated novel parameter informing true LV contractility. MW is calculated using echocardiography strain data, noninvasive BP measurements, and GE Healthcare proprietary software. There are four MW indices; here, we evaluated the global work index (GWI), the indexed total work performed by the LV through mechanical systole, including isovolumic relaxation and contraction. Purpose To describe our patient population diagnosed with sepsis with GWI calculated as part of their echocardiography. We also sought to compare the GWI values with GWI normal reference values reported in current literature to determine whether our observed mean GWI in a cohort of patients with sepsis deviates significantly from these established benchmarks in an average healthy population. Methods This report was a retrospective analysis of 179 consecutive patients ≥18 years with sepsis as defined by the Third International Consensus Definitions for Sepsis and Septic Shock who presented at our center from January 2020 to October 2023. LVEF (%) and GWI (mm Hg%) were reported as mean (±SD). A one-sample t-test was used to determine if the mean MWI for males and females diagnosed with sepsis at our center significantly differed from the reported GWI literature of reference patients without sepsis. Results Males (n=90, 50.3%) from our center had a significantly lower GWI mean (1353.06 ± 490.75) than the literature-reported male reference value of 2062 (P < 0.001) and a 95% confidence interval (1250 to 1455.84). See the Table. In 89 (49.7%) females with sepsis, mean GWI was also significantly lower, 1511 ± 595.79 (P < 0.001), than the normal reported female reference GWI value 2155 with a 95% CI (1385.57 to 1636.58). The pooled GWI mean was 1440.0±561.8 (ref: 2118±277). Septic males and females had preserved mean LVEF values of 51.6±13.11 and 56.8±14.4, respectively. The pooled mean LVEF was 54.0±13.8. Conclusion These findings revealed preserved LVEF alongside decreased global work index in patients with sepsis. To our knowledge, this is the first description of MW indices in septic patients. The results highlight the importance of further investigations into the role of MW indices in sepsis and the potential for these indices to enhance our understanding and clinical approach to myocardial dysfunction in sepsis.

Characteristics, clinical care, and outcomes of sepsis among patients boarding in the emergency department.

Patients who first meet clinical criteria for sepsis while boarding in the emergency department (ED) may not receive optimal sepsis care. Assess the association between ED boarding status and sepsis quality of care and outcomes. We conducted a retrospective cohort study of adult patients admitted to a large academic hospital from July 2021 to October 2023 who had clinical features consistent with sepsis present while physically in the ED. We compared outcomes for patients who experienced time zero (T-0; the time clinical features of sepsis were first present) while boarding in the ED (physically in the ED but admitted to a different service) to those experiencing T-0 while still under the care of the ED provider team. We used logistic regression to estimate the association between ED boarding status at T-0 and compliance with the US Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock: Management Bundle (SEP-1) core measure, individual bundle element compliance, and hospital mortality adjusting for prespecified covariates. In a subgroup analysis among patients who had not already received antibiotics before T-0, we conducted a Cox proportional hazards model to estimate the association between boarding status on time-to-antibiotics. Among 4795 patients meeting a clinical definition of sepsis in the ED, 422 (8.8%) experienced T-0 as ED boarders. These patients were similar in age, sex, and comorbidities compared with patients experiencing T-0 while still under ED care. Fewer patients with T-0 as an ED boarder received SEP-1 compliant care (25% vs. 38%, p < .001), including a lower proportion of fluid resuscitation (15% vs. 26%, p = .004) and lactate assessment (62% vs. 94%, p < .001). Overall, more patients in the ED boarder group received antibiotics within 3 hours, but one-third of patients had already received antibiotics prior to T-0. Among patients who had not already received antibiotics prior to T-0, experiencing T-0 as an ED boarder was associated with a decreased likelihood of receiving antibiotics (hazard ratio [HR]: 0.67 [95% confidence interval [CI], 0.54-0.84]) and longer time to antibiotics from T-0 (142 min vs. 100 min, p = .007). Sepsis patients experiencing T-0 as a boarder in the ED have a lower likelihood of receiving SEP-1 compliant care compared to patients who experience T-0 while still under ED care.

Interferon-gamma driven elevation of CXCL9: a new sepsis endotype independently associated with mortality

Endotype classification becomes the cornerstone of understanding sepsis pathogenesis. Macrophage activation-like syndrome (MALS) and immunoparalysis are the best recognized major endotypes, so far. Interferon-gamma (IFNγ) action on tissue macrophages stimulates the release of the cytotoxic chemokine CXCL9. It was investigated if this mechanism may be an independent sepsis endotype. In this cohort study, 14 patient cohorts from Greece, Germany and Italy were studied. The cohorts were 2:1 randomly split into discovery and validation sets. Sepsis was defined by the Sepsis-3 definitions and blood was sampled the first 24h from meeting the Sepsis-3 definitions. Concentrations of IFNγ, CXCL9, IP-10 (IFNγ induced protein-10), soluble CD163 and ferritin were measured. The endotype of IFNγ-driven sepsis (IDS) was defined in the discovery set as the combination of a) blood IFNγ above a specified cut-off associated with the minimal risk for immunoparalysis (defined as ≥8000 HLA-DR receptors on CD45/CD14-monoytes); and b) increase of CXCL9. Results were compared to the validation set. 5503 patients were studied; 3670 in the discovery set and 1833 in the validation set. IDS was defined as IFNγ more than 3pg/ml and CXCL9 more than 2200pg/ml. The frequency of IDS in the discovery set was 19.9% (732 patients; 95% confidence intervals-CIs 18.7-21.3%) and in the validation set 20.0% (366 patients; 95% CIs 18.2-21.9%). Soluble CD163, a marker of macrophage activation, was greater in IDS and IDS had features distinct from MALS. The mortality in IDS patients was 43.0% (315 patients; 95% CIs 39.5-46.6%) in the discovery set and 40.4% in the validation set (148 patients; 95% CIs 35.5-45.5%) (p=0.44 compared to patients of the discovery set). IDS was an independent risk factor for death in the presence of other endotypes, severity scores and organ dysfunctions of the multivariate model [hazard ratio 1.71 (95% CIs 1.45-2.01) in the discovery set and 1.70 (95% CIs 1.34-2.16) in the validation set]. Decreases of IFNγ and CXCL9 blood levels within the first 72h were associated with better outcome. IDS is a new sepsis endotype independently associated with unfavorable outcome. Hellenic Institute for the Study of Sepsis; Horizon 2020 project ImmunoSep; Swedish Orphan BioVitrum AB (publ) and German Federal Ministry of Education and Research.

Effect of heart rate control with ivabradine on hemodynamic in patients with sepsis: study protocol for a prospective, multicenter, randomized controlled trial

IntroductionSepsis, a life-threatening syndrome, is often accompanied by tachycardia in spite of hypovolemia and hypotension have been corrected. Recently, relevant studies have shown that sustained tachycardia in sepsis was related to high mortality, and appropriate control of heart rate (HR) could improve prognosis. Ivabradine reduces HR directly without a negative inotropic effect through inhibition of the If ionic current, which is different from the traditional rate control drug (beta-blockers).Methods and analysisThis is a prospective, multicenter, randomized, open label study designed to investigate the effect of heart rate control with ivabradine on hemodynamic in patients with sepsis. Our study will enroll 172 patients with sepsis as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria with sinus rate of 95 bpm or higher despite a hemodynamic optimization. Patients will be randomly assigned to standard treatment group (GS) or ivabradine group (GI, standard treatment for sepsis plus enteral ivabradine). Patients in GI will receive ivabradine to maintain HR between 70 and 94 bpm. The primary outcome is the difference of a reduction in HR below 95 bpm and the effect of ivabradine on hemodynamics between GI and GS group within the first 96 h after randomization. The secondary outcomes include organ function measures, the difference in SOFA score, incidence of adverse events, need for organ support, length of ICU stay, and 28-day overall mortality.DiscussionThere are limited studies on ivabradine to control heart rate in patients with sepsis. Our study aims to evaluate whether direct sinus node inhibition can improve hemodynamics, as well as its impact on organ function and prognosis in patients with sepsis, so as to provide evidence for the safe usage in clinical practice.Trial registrationClinicalTrials.gov NCT05882708. Registered on May 11, 2023, https://clinicaltrials.gov/ct2/show/NCT05882708.

Adjudication of Codes for Identifying Sepsis in Hospital Administrative Data by Expert Consensus.

Refine the administrative data definition of sepsis in hospitalized patients, including less severe cases. For each of 1928 infection and 108 organ dysfunction codes used in Canadian hospital abstracts, experts reached consensus on the likelihood that it could relate to sepsis. We developed a new algorithm, called AlgorithmL, that requires at least one infection and one organ dysfunction code adjudicated as likely or very likely to be related to sepsis. AlgorithmL was compared with four previously described algorithms, regarding included codes, population-based incidence, and hospital mortality rates-separately for ICU and non-ICU cohorts in a large Canadian city. We also compared sepsis identification from these code-based algorithms with the Centers for Disease Control's Adult Sepsis Event (ASE) definition. Among Calgary's adult population of 1.033 million there were 61,632 eligible hospitalizations. None. AlgorithmL includes 720 infection codes and 50 organ dysfunction codes. Comparison algorithms varied from 42-941 infection codes to 2-36 organ codes. There was substantial nonoverlap of codes in AlgorithmL vs. the comparators. Annual sepsis incidence rates (per 100,000 population) based on AlgorithmL were 91 in the ICU and 291 in the non-ICU cohort. Incidences based on comparators ranged from 28-77 for ICU to 11-266 for non-ICU cohorts. Hospital sepsis mortality rates based on AlgorithmL were 24% in ICU and 17% in non-ICU cohorts; based on comparators, they ranged 27-38% in the ICU cohort and 18-47% for the non-ICU cohort. Of AlgorithmL-identified cases, 41% met the ASE criteria, compared with 42-82% for the comparator algorithms. Compared with other code-based algorithms, AlgorithmL includes more infection and organ dysfunction codes. AlgorithmL incidence rates are higher; hospital mortality rates are lower. AlgorithmL may more fully encompass the full range of sepsis severity.

External validation of the Epic sepsis predictive model in 2 county emergency departments.

To describe the diagnostic characteristics of the proprietary Epic sepsis predictive model best practice advisory (BPA) alert for physicians in the emergency department (ED). The Epic Sepsis Predictive Model v1.0 (ESPMv1), a proprietary algorithm, is intended to improve provider alerting of patients with a likelihood of developing sepsis. This retrospective cohort study conducted at 2 county EDs from January 1, 2023 to December 31, 2023 evaluated the predictive characteristics of the ESPMv1 for 145885 encounters. Sepsis was defined according to the Sepsis-3 definition with the onset of sepsis defined as an increase in 2 points on the Sequential Organ Function Assessment (SOFA) score in patients with the ordering of at least one blood culture and antibiotic. Alerting occurred at an Epic recommended model threshold of 6. The ESPMv1 BPA alert was present in 7183 (4.9%) encounters of which 2253 had sepsis, and not present in 138702 encounters of which 3180 had sepsis. Within a 6-hour time window for sepsis, the ESPMv1 had a sensitivity of 14.7%, specificity of 95.3%, positive predictive value of 7.6%, and negative predictive value of 97.7%. Providers were alerted with a median lead time of 0 minutes (80% CI, -6 hours and 42 minutes to 12 hours and 0 minutes). In our population, the ESPMv1 alerted providers with a median lead time of 0 minutes (80% CI, -6 hours and 42 minutes to 12 hours and 0 minutes) and only alerted providers in half of the cases prior to sepsis occurrence. This suggests that the ESPMv1 alert is adding little assistance to physicians identifying sepsis. With clinicians treating sepsis 50% of the time without an alert, pop-ups can only marginally assist in disease identification. The ESPMv1 provides suboptimal diagnostic characteristics for undifferentiated patients in a county ED.